HPV vaccine: A key cervical cancer prevention strategy

The world has a population of nearly three billion women aged 15 years and older who are at risk of developing cervical cancer. Worldwide cervical cancer ranks the fourth most common cancer among women and the second most common cancer deaths in women aged 15-44 years. In Ireland there are 295 cases of invasive cancer each year and 3,213 cases of cervical cancer in situ.¹ Yearly, more than 6,500 women are diagnosed with high grade cervical intraepithelial neoplasia (CIN) and require treatment at one of the 15 national CervicalCheck colposcopy clinics.²

Human papillomavirus (HPV) is understood to play a definite role in the development of cervical cancer. It is a necessary but not a sole causative agent. Some 99.7 % of cervical cancers contain high risk HPV DNA.³

HPV is a large family of double stranded DNA viruses. Approximately 40 of these can infect the genital tract and 14 are recognised as high risk oncogenic HPV. HPV 16 and 18 are associated with 70% of cervical cancers worldwide. HPV is an extremely common infection. It is estimated that 80% of women will become infected within 18 months of becoming sexually active. The vast majority of infected individuals mount an effective immune response becoming HPV negative within a further 18 months with subsequent sustained clinical remission from disease. In a minority of women the infection can persist. Contributing factors for the development of cervical cancer include cigarette smoking, which lowers the immune response, and immune suppression. 

Screening

The two main preventative strategies for cervical cancer in Ireland are screening and vaccination. CervicalCheck is an organised, population-based and quality-assured screening programme. CervicalCheck is designed to detect signs that disease may develop in women who are within the at risk population. Approximately 1.2 million women who are resident in Ireland aged 25 to 60 are eligible for screening. For women aged 25 to 44, tests are offered at three-yearly intervals. For women aged 45 to 60, the interval changes to five yearly following two consecutive negative results. A call/recall system is in place and the result of the screening test or treatment at colposcopy discharge recommendation determines when women will be recalled. 

The levels of engagement with CervicalCheck needs to remain high, (greater than 80% coverage of the target population) in order to achieve the goal of impacting on cervical cancer. To date the overall number of women screened by CervicalCheck is high (79.6%) we are aware that currently one in five women are not attending for screening. We would like to increase uptake further especially in counties where uptake is lower. Women in Clare Laois, Kilkenny, Monaghan, Offaly and Roscommon are less likely to attend as are women over the age of 50 years.⁴  Health professionals are challenged to promote and facilitate continued participation of all eligible women. 

GP Practices rank the highest (76%) for women sourcing information about their screening needs and health. Therefore doctors and nurses should continue to use every opportunity to provide women with appropriate information about their screening needs.⁵ Healthcare professionals should remember to check a woman’s cervical screening status; ask if they are up to date with cervical screening, remind and encourage women to attend and facilitate women’s engagement with screening. 

Evidence shows that women who have a positive experience when attending for a cervical screening test are more likely to continue to participate in the programme.⁶ A screening test is not a test for cancer; currently the test involves cytology as the primary screening tool, and may involve a HPV type assessment. Remember a screening test is not a diagnostic test. A screening test is not recommended on a woman who is symptomatic, further investigation and a gynaecology referral should be considered.

The Health information and Quality Authority (HIQA) is currently conducting a Health Technology Assessment (HTA) on HPV technologies before  the introduction of HPV testing as the Primary screening strategy for CervicalCheck. The HTA will address and inform on screening strategies, tools, age range and screening intervals; changing the landscape of Ireland’s cervical screening programme significantly in the future. This will impact the CervicalCheck programme, contracted laboratories, colposcopy clinics, nurses and doctors who perform cervical screening and eligible women. 

Vaccine

Recognition of the role of oncogenic HPV in the genesis of cancer of the cervix prompted the development of a vaccine against the most commonly recognised oncogenic types. There is evidence that  HPV vaccines prevent cervical cancer.⁷

The HPV vaccine is recommended by the WHO, the American Society for Clinical Oncology, the International Federation of Obstetricians and Gynaecologists and the expert Immunisation body in Ireland to reduce the burden of cervical cancer in women.⁸

There are three licensed HPV vaccines: 

• HPV 2 Cervarix vaccinates against types 16,18, causing 70% of cervical cancers

• HPV4 Gardasil vaccinates against HPV types 6, 11, 16, 18, two of which cause 70% cervical cancers and 6 and 11 causing warts

• HPV9 vaccinates against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 59, seven of which cause 90% cervical cancers.

Since 2006, countries that have started HPV vaccination programmes with high uptake rates have revealed a reduction in high grade cervical intraepithelial neoplasia (CIN), with Scotland and Denmark showing a reduction of more than 50%.^9,10  There was also a fall in incidence of anogenital warts in vaccinated girls under 21 in Australia from 18% to 1.1 %.¹¹

HPV4 vaccine (Gardasil) is used in the HSE HPV school vaccination programme in Ireland since 2010. 

• It is licensed to prevent premalignant genital lesions and cervical cancer related to HPV types 16 and 18

• All girls less than 15 years of age require two doses of HPV vaccine given at zero and six months

• All girls aged 15 years and up to the age of 26 and people with weakened immune systems require three doses of HPV vaccine given at zero, two and six months

• The duration of efficacy of the HPV vaccines is likely to give long-term protection. Delere et Al’s meta-analysis of vaccine protection against Human Papilloma virus showed 84% efficacy and duration >6 years and is likely to predict long-term efficacy duration.¹²

Remember cervical screening should continue in the vaccinated cohort as to date the vaccines only protect against 70% of oncogenic HPV types.

Boys are currently not vaccinated but it’s worth noting that HPV is also responsible for more than 90% of anal cancers, more than 40% of penile cancers and more than  35% of oropharyngeal cancer.¹³ There is a case for vaccinating boys as herd immunity would confer protection from vaccinated to unvaccinated people.

Schools

The HSE HPV school vaccination programme is recommended for all girls aged 12-13 years and ideally the HPV4 Gardisil vaccine should be given before exposure to HPV virus at sexual contact. The HSE HPV schools programme distributes information leaflets, consent forms and contacts to parents in advance of administering the vaccination.¹⁴ Factsheets are also available from the National Immunisation office on ‘HPV Vaccine Key Facts’ for GPs and ‘HPV Vaccines and Cervical Cancer’ for school principals.¹⁵

More than 220 million doses of HPV4 (Gardasil) have been distributed in more than 29 countries worldwide. In Ireland in excess of 220,000 girls have been fully vaccinated by HPV school vaccination teams. The vaccination programme in Ireland aims to achieve a high uptake of over 80% for a completed vaccine course. Until 2015, the uptake rate was high; 2014/15 saw an 87% uptake following two doses with an impressive cohort retention record of over 97%.¹⁵

Concern

However parents started to raise concerns about vaccine safety in 2015 following local and national media coverage alleging that the HPV vaccine was unsafe. The safety profile of the HPV vaccine has been monitored since 2006 by the WHO Global Advisory Committee on Vaccine Safety (GACVS), the European medicines agency (EMA) and other international bodies.

The World Health Organization GACVS has reviewed the evidence on the safety of Gardasil vaccine and concluded in December 2015 that Gardasil continues to have an excellent safety profile.¹⁶ In November 2015 the EMA reported following a review of HPV vaccines found no evidence there was any causal relationship between the HPV vaccine and chronic-fatigue-like conditions. 

In January 2016 the EMA issued a final report on this review of HPV vaccines: “EMA confirms evidence does not support that they cause complex regional pain syndrome or postural orthostatic tachycardia syndrome.”¹⁷ No scientific evidence of an increased link in incidence of long-term medical conditions and the vaccine has been established to date.

Alarm

In Ireland and other jurisdictions the anti HPV vaccine narrative has led to a drop in public confidence and negatively influenced the decision making of parents. The eroded confidence in the HPV vaccine and authorities delivering them has led not only to vaccine hesitancy but has dramatically impacted on the HPV vaccination uptake rate in Ireland. The 2015/16 uptake rates were reduced to 72% and 2016/17 rates is estimated by the National Immunisation office, at 50% following first dose of vaccine, down in all areas nationally. The reduced rates are believed to be directly related to the vaccine safety scare. It would be a shame if avoiding the risks associated with the HPV vaccine were to become more important than benefiting from the protection the vaccine has to offer. This is an alarming concern for health care professionals in cervical cancer prevention.

Healthcare professionals will be asked questions by concerned parents and the public such as: does HPV cause cervical cancer; does HPV vaccination prevent HPV infection and cervical cancer; and is it safe? The evidence to date suggests yes to all three questions. There is no doubt HPV vaccination is both safe and effective.

HPV vaccination coupled with the cervical screening programme has the potential to prevent women from developing cervical cancer. All healthcare professionals play a vital role in the promotion of the HPV vaccine and cervical screening. The recommendation of a trusted health professional leads to increased vaccine and screening uptake. Resources are available from CervicalCheck and the National Immunisation office to support informed consent in a way the public can understand about the safety and effectiveness of the HPV vaccine and cervical screening. 

The author challenges health professionals to become advocates for cervical screening and HPV vaccination. Combined screening and vaccination has the potential to save young women’s lives. 

The author would like to acknowledge the kind assistance of Criona Burns, GP advisor, CervicalCheck (NSS) in compiling this article.

References

1. National Cancer Registry, Ireland fact sheet: http://www.ncri.ie/sites/ncri/files/factsheets/FACTSHEET_cervix_2.pdf 
2. CervicalCheck-The National Cervical Screening Programme Report 2014/15
3. Zur Hausen H. Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis. J National Cancer Institute (2000) 92 (9): 690-698. Published 03 May 2000
4. CervicalCheck Programme report 2014/15
5. NSS Omnibus Benchmark Evaluation of Key Programmes, MillWardBrown Study 2016
6. Walsh J. (2003): Factors affecting Attendance for a Cervical Smear Test: A Prospective study. Collaboration between Irish Cervical Screening Programme and the National University of Ireland, Galway. (Psychology Dept.)
7. Koutsky LA et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002;347:1645-51
8. http://www.immunisation.ie
9. Pollock KG, Kavanagh K Potts A et al. Reduction of low and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland. Br J Cancer 2014; 111:1824-1830
10. Baldur-Felskov B, Dehlendorff C, Munk C, Kjaer K. Early Impact of human kapillomavirus vaccination on cervical neoplastic- nationwide follow-up of young Danish women. J Natl Cancer Inst 2014; 106 (3):djt460
11. Hammond A, Donovan B, Wand H et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ 2013; 346:f2032
12. Deleré Y et al. The efficacy and duration of vaccine protection against human papillomavirus a systematic review and meta-analysis. Dtsch Arztebl Int. 2014 Sep; 111(35-36): 584–591.13 Muñoz N, Castellsague X, de Gonzalez AB et al. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006;24 (Suppl 3):S1-10
13. www.hpv.ie
14. www.immunisation.ie
15. http://www.who.int/vaccine_safety/committee/GACVS_HPV_statement_17Dec2015.pdf?ua=1) 
16. (http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/HPV_vaccines_20/European_Commission_final_decision/WC500196773.pdf)